Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa

Giulio Macchiarella, Vanessa Cornacchione, Celine Cojean, Julia Riker, Yichen Wang, Helene Te, Melanie Ceci, Johann E. Gudjonsson, Swann Gaulis, Jean François Goetschy, Audrey Wollschlegel, Stephanie K. Gass, Sofia Oetliker-Contin, Barbara Wettstein-Ling, Dirk J. Schaefer, Pascale Meschberger, Roland de Roche, Rik Osinga, Grazyna Wieczorek, Ulrike NaumannJoachim C.U. Lehmann, Anna Schubart, Andreas Hofmann, Lukas Roth, Edwin F. Florencia, Christian Loesche, Elisabetta Traggiai, Alexandre Avrameas, Errol P. Prens, Till A. Röhn, Ben Roediger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients’ QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.

Original languageEnglish
Pages (from-to)273-283.e12
JournalJournal of Investigative Dermatology
Volume143
Issue number2
DOIs
Publication statusE-pub ahead of print - 15 Sep 2022

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